Tonic activity of Galpha-gustducin regulates taste cell responsivity.
The taste-selective G protein, alpha-gustducin (alpha-gus) is homologous to alpha-transducin and activates phosphodiesterase (PDE) in vitro. alpha-Gus-knockout mice are compromized to bitter, sweet and umami taste stimuli, suggesting a central role in taste transduction. Here, we suggest a different role for Galpha-gus. In taste buds of alpha-gus-knockout mice, basal (unstimulated) cAMP levels are high compared to those of wild-type mice. Further, H-89, a cAMP-dependent protein kinase inhibitor, dramatically unmasks responses to the bitter tastant denatonium in gus-lineage cells of knockout mice. We propose that an important role of alpha-gus is to maintain cAMP levels tonically low to ensure adequate Ca2+ signaling.
Clapp
Tod R
TR
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, United States.
Trubey
Kristina R
KR
Vandenbeuch
Aurelie
A
Stone
Leslie M
LM
Margolskee
Robert F
RF
Chaudhari
Nirupa
N
Kinnamon
Sue C
SC
D000818:Animals; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013649:Taste; D013650:Taste Buds / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*
D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D000644:Quaternary Ammonium Compounds; D013449:Sulfonamides; D000242:Cyclic AMP; C524407:GNAT3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins; C053525:denatonium saccharide; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide